Total synthesis and cytotoxicity of (−)-jorumycin and its analogues

(−)-Jorumycin and its 15 C-22 analogues were prepared employing l-tyrosine as the chiral starting material via 21 steps. These analogues, along with (−)-jorumycin itself, were evaluated in vitro for cytotoxicity against HCT-8, BEL-7402, Ketr3, A2780, MCF-7, A549, BGC-823, Hela, HELF, and KB cells. The IC50 values of the cytotoxicity of most of these analogs were at the level of nM, which was similar to that of (−)-jorumycin. Among these analogs including (−)-jorumycin, hippuric acid ester derivative 23 exhibited the most potent and broad-spectrum cytotoxic activity against the ten cell lines with an average IC50 of 2.12 nM.